Absorption, distribution and excretion of GT31-104, a novel bile acid sequestrant, in rats and dogs after acute and subchronic administration

The absorption, distribution, and excretion of GT31-104, a novel bite acid sequestrant, was studied in rats and dogs after both acute and subchronic oral administration. The polyallylamine backbone of GT31-104 was labeled with tritium and one of the alkyl side chains was labeled with C-14. The mean blood and plasma concentration of [H-3, C-14]GT31-104 in rats, in both treatment regimens, was negligible at all time points, with the highest amount observed being 0.69 mu g eq/g blood; in dogs the mean blood and plasma concentration of [H-3, 14C]GT31-104 was below the limit of quantitation (<0.001% total dose) at all time points. In both rats and dogs, the mean total urinary excretion of [H-3, C-14]GT31-104 was similar to 0.06% of the total dose. The fecal excretion data indicates that both H-3- and C-14-derived radioactivity was excreted entirely in the feces. Mean total radioactivity excreted in the feces ranged from similar to 95 to 105% in the rats and 92 to 102% in the dogs. Across the different treatment regimens, in both species, tissue concentrations were negligible (<0.01% total dose) and no differences in tissue profile were noted, indicating that there was no effect of pretreatment on [H-3, C-14]GT31-104 absorption. GT31-104 was extracted with water, and the water-soluble portion contained radioactivity that would correlate to similar to 0.19% of the H-3 dose and 0.41% of the C-14 dose; this portion probably accounted for the negligible radioactivity observed systemically. Analysis of gastrointestinaI (GI) tract tissues with contents indicated that GT31-104 is rapidly cleared from the GI tract. These data indicate that GT31-104 is not absorbed from the GI tract in rats and dogs.